Perhaps an organization that exists in both the Naruto world and the alchemist world. They might see the combination of Naruto and the alchemist as a threat to their plans of world domination. So they become the main antagonist, trying to stop Naruto and the alchemist from teaming up and using their combined powers.
It could be a powerful alchemist who has gone rogue and wants to use Naruto's chakra for some dark alchemy purpose.
Another possibility is a being from the alchemist world that is corrupted by the idea of chakra. This being might think that by consuming Naruto's chakra, it can gain ultimate power and break all the rules of alchemy. So it sets out to capture Naruto, becoming the main force that Naruto and his new alchemist friend have to fight against.
Maybe a powerful rogue ninja who has discovered a way to steal the powers of divine entities. He sets his sights on Amaterasu and Naruto because he knows that if he can combine their powers, he will be unstoppable. He creates various traps and illusions to separate them and weaken them so that he can carry out his evil plan.
It could be someone who wants to steal Samehada for its power. Maybe a rogue ninja who has heard of Samehada's ability to absorb chakra and plans to use it to take over the ninja world.
It could be an evil ninja who wants to capture the fem Kyuubi for her power. He might see the unique bond between Naruto and the fem Kyuubi as a threat to his plans of world domination.
Maybe Orochimaru could be the antagonist. He hears about Naruto's encounter with Yagura and wants to use their connection for his own evil experiments. He might try to capture Yagura again (if he was once under Orochimaru's control) or manipulate Naruto into doing something that would harm Yagura and the relationship between the two villages.
It could be an evil shinobi who wants to disrupt the meeting between Naruto and Kushina. Maybe they know that Kushina has some special knowledge or power that she could pass on to Naruto, and they don't want that to happen.
It could be a rogue Sound ninja who has his own agenda. Maybe he wants to start a war between Konoha and the Sound Village to gain power in the chaos. He would see Naruto as a threat to his plans and try to eliminate him.
It could be someone who doesn't want Naruto and his sister to unite. Maybe a rogue ninja who fears their combined power. He might try to drive a wedge between them by spreading false rumors or causing misunderstandings.
It could be a rogue ninja who is after Sakumo's hidden techniques. Since Naruto meets Sakumo, this rogue ninja sees Naruto as an obstacle and tries to eliminate him. This antagonist might have a grudge against the Hatake clan and wants to use Sakumo's secrets for his own evil purposes.
In such a fanfiction, Naruto might learn about alchemy. Maybe he would be intrigued by the concept of transmutation and try to incorporate it into his ninja skills. For example, he could use alchemy to create new weapons or tools on the fly during battles.
Maybe a rogue ninja who has somehow tapped into dark powers related to Kami's domain. This ninja wants to use these powers to take over the ninja world, and Naruto, with Kami's help, has to stop him. In this fanfiction, the rogue ninja could have some personal vendetta against Kami as well, which adds more depth to the story.